Diets rich in fruits and vegetables (FV), which contain (poly)phenols, protect against age-related inflammation and chronic diseases. T-lymphocytes contribute to systemic cytokine production and are modulated by FV intake. Little is known about the relative potency of different (poly)phenols in modulating cytokine release by lymphocytes. We compared thirty-one (poly)phenols and six (poly)phenol mixtures for effects on pro-inflammatory cytokine release by Jurkat T-lymphocytes. Test compounds were incubated with Jurkat cells for 48 h at 1 and 30 µm, with or without phorbol ester treatment at 24 h to induce cytokine release. Three test compounds that reduced cytokine release were further incubated with primary lymphocytes at 0·2 and 1 µm for 24 h, with lipopolysaccharide added at 5 h. Cytokine release was measured, and generation of H2O2 by test compounds was determined to assess any potential correlations with cytokine release. A number of (poly)phenols significantly altered cytokine release from Jurkat cells (P<0·05), but H2O2 generation did not correlate with cytokine release. Resveratrol, isorhamnetin, curcumin, vanillic acid and specific (poly)phenol mixtures reduced pro-inflammatory cytokine release from T-lymphocytes, and there was evidence for interaction between (poly)phenols to further modulate cytokine release. The release of interferon-γ induced protein 10 by primary lymphocytes was significantly reduced following treatment with 1 µm isorhamnetin (P<0·05). These results suggest that (poly)phenols derived from onions, turmeric, red grapes, green tea and açai berries may help reduce the release of pro-inflammatory mediators in people at risk of chronic inflammation.